One of the most formidable obstacles in the development of an effective anti-HIV vaccine is our lack of knowledge on how best to present HIV antigens to the immune system to develop protective immune responses. Specifically, the generation by immunization of vigorous neutralizing antibody responses in animals and humans against the HIV envelope, a natural target for immune responses during HIV infection, has been proven to be an extremely difficult tasks. It is possible that previous immunization attempts to elicit neutralizing antibodies gains the HIV envelope have failed to do so because the envelope form used as immunogen was different from the existing of the surface of infectious HIV virions or HIV-infected cells. AN additional possibility for the lack of generation of neutralizing antibodies is that the administered envelope proteins were inefficiently delivered to the appropriate immune cells. To address these possibilities, we propose to immunize macaques with a form of the HIV envelope that mimics that found on the surface of primary HIV isolates and test various methodologies for their potential to optimize the delivery of our immunogen to relevant immune cells. We will monitor the generation of neutralizing antibodies in the blood and vaginal mucosa. FUNDING AmFAR (02572) PUBLICATIONS None